Genetics and Genomics of Neuromuscular and Neurodegenerative Disorders

TREAT-CMT researchers describe the relationship between the NRG1 / ErbB route myelination and neuropathy Charcot-Marie-Tooth (CMT)

Doctors Carmen Espinós and Francesc Palau, the U732 CIBERER and Prince Felipe Research Center, participated in research published in GLIA on the relationship between the NRG1 / ErbB and route CMT conducted jointly with the group led by Dr. Roman Chrast at the University of Lausanne. This work is the result mainly of stay of Dr. Vincenzo Lupo, CIBERER researcher in the laboratory of Dr. Chrast.

Mutations in the gene cause SH3TC2 CMT demyelinating neuropathy 4C autosomal recessive (CMT4C). SH3TC2 is specifically expressed in Schwann cells and is necessary for proper myelination of peripheral axons. In line with earlier onset of neuropathy observed in patients with CMT4C, studies of the mouse model of CMT4C made in this investigation have shown that the properties of myelinating Schwann cells deficient in SH3TC2 are affected at an early stage. This phenotype is associated with early changes in the canonical pathway NRG1 / ErbB involved in controlling myelination.

Responsible for the research have shown that ErbB2 SH3TC2 interacts with and plays a role in the regulation of intracellular trafficking ErbB2 from the plasma membrane upon activation by NRG1. SH3TC2 both function loss in mice as pathological mutations present in patients CMT4C affect internalization of ErbB2, potentially altering the subsequent intracellular signaling pathways. Overall, the results indicate that the molecular mechanism for detecting the size axon is disturbed in myelinating Schwann cells deficient in SH3TC2-deficient, thus providing a new understanding of the pathophysiology of the neuropathy CMT4C.

GLIA article